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Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid organ cancers

Scurr, Martin, Zelek, Wioleta, Lippiatt, George, Somerville, Michelle, Burnell, Stephanie, Capitani, Lorenzo, Davies, Kate, Lawton, Helen, Tozer, Thomas, Rees, Tara, Roberts, Kerry, Evans, Mererid, Jackson, Amanda, Young, Charlotte, Fairclough, Lucy, Tighe, Paddy, Wills, Mark, Westwell, Andrew, Morgan, Bryan Paul, Gallimore, Awen and Godkin, Andrew 2022. Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid organ cancers. Immunology 165 (2) , pp. 250-259. 10.1111/imm.13433

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Abstract

Accurate assessment of SARS-CoV-2 immunity is critical to evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimised a high-throughput whole blood-based assay to determine the T cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH1-type cytokines. Highly significant differential IFN-γ+/IL-2+ SARS-CoV-2-specific T cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison to unknown / naïve individuals (P<0.0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96.0% vs. 83.3%) but lower specificity (84.4% vs. 92.5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T cell responses in 116/128 (90.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P<0.0001). A second dose was sufficient to boost T cell responses in the majority (90.6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (P=0.034). Three-month post-vaccination T cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardisable test ensures accurate and comparable assessments of SARS-CoV-2-specific T cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Pharmacy
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License
Publisher: Wiley
ISSN: 0019-2805
Date of First Compliant Deposit: 11 November 2021
Date of Acceptance: 17 September 2021
Last Modified: 20 Jan 2022 10:54
URI: http://orca.cardiff.ac.uk/id/eprint/145428

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